Dr. Chatila and his associates have recently identified two patients with severe combined immunodeficiency (SCID) caused by defective production of the T cell growth factor Interleukin 2 (IL-2). In this application he proposes to study the molecular basis of this deficiency by first determining whether the defective production of IL-2 is due to a defect at the transcriptional level (such as gross gene deletions, failure of initiation of transcription (secondary to cis- or trans-acting mutations affecting the 5' Il-2 regulatory region) or a posttranscriptional defect (failure of IL-2 mRNA translation, enhanced IL-2 mRNA degradation, enhanced nascent IL-2 protein degradation, failure of Il-2 export, or the production of an IL-2 protein with reduced or absent biologic activity). He also plans to investigate the capacity of the patients' T cells to produce lymphokines other than IL-2 (which, if deficient, would suggest a trans-acting defect at the transcriptional level). In the case of cis-acting defects, he will attempt to identify the genetic abnormality using genomic and/or cDNA cloning techniques. The methods used will include classic molecular biologic techniques.